Olson, HE;
Demarest, ST;
Pestana-Knight, EM;
Swanson, LC;
Iqbal, S;
Lal, D;
Leonard, H;
... Benke, TA; + view all
(2019)
Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review.
[Review].
Pediatric Neurology
, 97
pp. 18-25.
10.1016/j.pediatrneurol.2019.02.015.
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Abstract
CDKL5 deficiency disorder (CDD) is a developmental encephalopathy caused by pathogenic variants in the gene cyclin-dependent kinase-like 5 (CDKL5). This unique disorder includes early infantile onset refractory epilepsy, hypotonia, developmental intellectual and motor disabilities, and cortical visual impairment. We review the clinical presentations and genetic variations in CDD based on a systematic literature review and experience in the CDKL5 Centers of Excellence (COEs). We propose minimum diagnostic criteria. Pathogenic variants include deletions, truncations, splice variants, and missense variants. Pathogenic missense variants occur exclusively within the kinase domain or affect splice sites. The CDKL5 protein is widely expressed in the brain, predominantly in neurons, with roles in cell proliferation, neuronal migration, axonal outgrowth, dendritic morphogenesis and synapse development. The molecular biology of CDD is revealing opportunities in precision therapy, with phase 2 and 3 clinical trials underway or planned to assess disease specific and disease modifying treatments.
| Type: | Article |
|---|---|
| Title: | Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.pediatrneurol.2019.02.015 |
| Publisher version: | https://doi.org/10.1016/j.pediatrneurol.2019.02.01... |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | CDKL5 deficiency disorder; developmental encephalopathy; epileptic encephalopathy; epilepsy genetics; clinical trials |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10072095 |
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